This project seeks to determine the function of the autonomic nervous system in the maintenance of lacrimal gland structure and in the secretion of lacrimal gland proteins. The structure and function of the lacrimal gland will be studied in normal, sympathectomized, and parasympathectomized rabbits. Additionally, attempts to inhibit or reverse the changes induced by denervation will be made by subcutaneous implantation of slow release, osmotic minipumps that will deliver directly to the lacrimal gland, autonomic agonists appropriate to the denervation experienced. Unilateral lacrimal sympathectomy will be by superior cervical ganglionectomy. Parasympathectomy will be attempted by cauterization of the facial nerve. Chemical sympathectomy will be by systemic release of atropine from subcutaneous or intraperitoneal minipump or by direct delivery to the lacrimal gland via a catheter attached to the minipump. Tear flow rates will be measured by fluorophotometry. Changes in lacrimal gland structure will be assessed by light microscopy and by autoradiography of 3H-ouabain binding to Na ion/K ion-ATPase. Secretion of lacrimal proteins will be measured in vitro using isolated lobules stimulated with cholinergic and adrenergic agonists. Differences in the proteins secreted into the medium will be determine by gel electrophoresis. Certain proteins such as IgG, secretory IgA, and secretory component will be quantitatively assayed by radial immunodiffusion. The capacity of isolated lacrimal cells to respond to autonomic agonists will be tested in cells recovered by enzymatic dissociation of normal and denervated glands. Changes in the membrane bound autonomic receptors due to denervation will be assayed in particulate fractions of homogenized cells. The receptors will be identified and quantitated by binding of specific radiolabelled ligands. These denervation methods for autonomic control of lacrimal gland will provide a basis for understanding lacrimal secretions in healthy and diseased states. The development of methods to deliver drugs in situ to the gland may provide new ways to treat dry eyes and other diseases of the ocular anterior segment.